Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program OVERALL PROJECT SUMMARY Chronic pain is a major health concern and one of the most common reasons adults seek medical care. It is associated with substantial morbidity linked to reduced quality of life, restricted mobility, depression, and opioid dependence. The biological mechanisms that prevent the resolution of acute pain after the initial insult and drive the transition from acute to chronic pain are poorly understood. The lack of rigorously validated biomarkers to predict which patients are more susceptible to the transition from acute to chronic pain states is thus a major gap hindering the development and implementation of population-wide and individualized preventive pain interventions. In the A2CPS Consortium, the Clinical Centers will recruit and collect clinical data and biofluid samples from two longitudinal cohorts of 1800 subjects each. Biofluid samples will be collected 0, 3, and 6 months after an acute pain episode, consisting of a specific surgical procedure or a specific musculoskeletal trauma. These samples will be used to generate multi-omic data to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain, as well as to identify new candidate biomarkers. For the proposed A2CPS Omics Data Generation Center (ODGC), Aim 1, which will be executed in Year 1, will involve close collaboration with other components of the A2CPS Consortium to establish the final study design and protocols. All of the A2CPS Program investigators will work together to establish the 40 primary outcome biomarkers. The ODGC and Clinical Center investigators will jointly decide on the specific sample type(s) and collection/processing/storage methods. The ODGC and Data integration Resource Center/Data Coordination Component (DIRC/DCC) investigators will establish Metadata and Data Standards and a workflow for submission of metadata and raw data to the DCC. The Administrative Core of the ODGC will establish a LIMS for sample and data tracking and recording of metadata. The ODGC will work closely with the DIRC/Data Integration and Analysis Component (DIAC) to establish data analysis pipelines. ODGC investigators also anticipate participating in integrative analyses with the DIRC/DIAC aimed at developing pain signatures comprised of multiple biomarker types (including molecular, clinical, psychosocial, and/or imaging biomarkers) indicating susceptibility/resilience to chronic pain, which can be used to develop personalized strategies for prevention and treatment of chronic pain. Aims 2 and 3 will span Years 2-4, with Aim 2 focused on data generation from the ~11,000 biofluid samples that will be collected by the Clinical Centers. Aim 3 will encompass submission of metadata and data to the DIRC/DCC, quality control of the data, and data analysis and interpretation. The primary goal of this project is to establish the A2CPS Omics Data Generation Center to generate genetic variant, metabolomic, lipidomic, proteomic, exRNA, transcriptome, and microbiome data from two pain cohorts to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain and identify novel biosignatures predicting the transition from acute to chronic pain.